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Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Valproic Acid and Epilepsy: From Molecular Mechanisms to Clinical Evidences

Author(s): Michele Romoli, Petra Mazzocchetti, Renato D'Alonzo, Sabrina Siliquini, Victoria Elisa Rinaldi, Alberto Verrotti, Paolo Calabresi and Cinzia Costa*

Volume 17, Issue 10, 2019

Page: [926 - 946] Pages: 21

DOI: 10.2174/1570159X17666181227165722

Price: $65


After more than a century from its discovery, valproic acid (VPA) still represents one of the most efficient antiepileptic drugs (AEDs). Pre and post-synaptic effects of VPA depend on a very broad spectrum of actions, including the regulation of ionic currents and the facilitation of GABAergic over glutamatergic transmission. As a result, VPA indirectly modulates neurotransmitter release and strengthens the threshold for seizure activity. However, even though participating to the anticonvulsant action, such mechanisms seem to have minor impact on epileptogenesis. Nonetheless, VPA has been reported to exert anti-epileptogenic effects. Epigenetic mechanisms, including histone deacetylases (HDACs), BDNF and GDNF modulation are pivotal to orientate neurons toward a neuroprotective status and promote dendritic spines organization. From such broad spectrum of actions comes constantly enlarging indications for VPA. It represents a drug of choice in child and adult with epilepsy, with either general or focal seizures, and is a consistent and safe IV option in generalized convulsive status epilepticus. Moreover, since VPA modulates DNA transcription through HDACs, recent evidences point to its use as an anti-nociceptive in migraine prophylaxis, and, even more interestingly, as a positive modulator of chemotherapy in cancer treatment. Furthermore, VPA-induced neuroprotection is under investigation for benefit in stroke and traumatic brain injury. Hence, VPA has still got its place in epilepsy, and yet deserves attention for its use far beyond neurological diseases. In this review, we aim to highlight, with a translational intent, the molecular basis and the clinical indications of VPA.

Keywords: Valproic acid, epilepsy, epileptogenesis, neuroprotection, pharmacology, epigenetics.

Graphical Abstract
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